Journal article
Genome-wide screening and identification of antigens for rickettsial vaccine development
FEMS immunology and medical microbiology, Vol.64(1), pp.115-119
02/2012
Handle:
https://hdl.handle.net/2376/113139
PMCID: PMC3288579
PMID: 22066488
Abstract
The capacity to identify immunogens for vaccine development by genome-wide screening has been markedly enhanced by the availability of microbial genome sequences coupled to proteomic and bioinformatic analysis. Critical to this approach is
in vivo
testing in the context of a natural host-pathogen relationship, one that includes genetic diversity in the host as well as among pathogen strains. We aggregate the results of three independent genome-wide screens using
in vivo
immunization and protection against
Anaplasma marginale
as a model for discovery of vaccine antigens for rickettsial pathogens.
In silico
analysis identified 62 outer membrane proteins (Omp) from the 949 predicted proteins in the
A. marginale
genome. These 62 Omps were reduced to 10 vaccine candidates by two-independent genome-wide screens using IgG2 from vaccinates protected from challenge following vaccination with outer membranes (screen 1) or bacterial surface complexes (screen 2). Omps with broadly conserved epitopes were identified by immunization with a live heterologous vaccine,
A. marginale ss. centrale
(screen 3), reducing the candidates to three. The genome-wide screens identified Omps that have orthologues broadly conserved among rickettsial pathogens, highlighted the importance of identifying immunologically sub-dominant antigens, and supported the use of reverse vaccinology approaches in vaccine development for rickettsial diseases.
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Details
- Title
- Genome-wide screening and identification of antigens for rickettsial vaccine development
- Creators
- Guy H Palmer - Program in Vector-borne Diseases, Department of Veterinary Microbiology and Pathology and The Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington 99164 USAWendy C Brown - Program in Vector-borne Diseases, Department of Veterinary Microbiology and Pathology and The Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington 99164 USASusan M Noh - Program in Vector-borne Diseases, Department of Veterinary Microbiology and Pathology and The Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington 99164 USAKelly A Brayton - Program in Vector-borne Diseases, Department of Veterinary Microbiology and Pathology and The Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington 99164 USA
- Publication Details
- FEMS immunology and medical microbiology, Vol.64(1), pp.115-119
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
- Grant note
- R37 AI044005-14 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Identifiers
- 99900548007401842
- Language
- English
- Resource Type
- Journal article